3ZQT

TARGETING THE BINDING FUNCTION 3 SITE OF THE ANDROGEN RECEPTOR THROUGH IN SILICO MOLECULAR MODELING

Summary for 3ZQT

• Entry DOI: 10.2210/pdb3zqt/pdb
• Related: 1E3G 1GS4 1T5Z 1T63 1T65 1XJ7 1XOW 1XQ3 1Z95 2AM9 2AMA 2AMB 2AO6 2AX6 2AX7 2AX8 2AX9 2AXA 2YHD 2YLO 2YLP 2YLQ
• Descriptor: ANDROGEN RECEPTOR, TESTOSTERONE, SULFATE ION, ... (5 entities in total)
• Functional Keywords: transcription, small molecule inhibitor
• Biological source: ESCHERICHIA COLI
• Cellular location: Nucleus: P10275
• Total number of polymer chains: 1
• Total formula weight: 30555.80

Authors

Lack, N.A.,Axerio, P.,Tavassoli, P.,Kuchenbecker, K.,Han, F.Q.,Chan, K.H.,Feau, C.,LeBlanc, E.,Tomlinson, E.,Guy, R.K.,Rennie, P.S.,Cherkasov, A. (deposition date: 2011-06-10, release date: 2011-12-07, Last modification date: 2023-12-20)

Primary citation

Lack, N.A.,Axerio-Cilies, P.,Tavassoli, P.,Han, F.Q.,Chan, K.H.,Feau, C.,Leblanc, E.,Guns, E.T.,Guy, R.K.,Rennie, P.S.,Cherkasov, A.
Targeting the Binding Function 3 (Bf3) Site of the Human Androgen Receptor Through Virtual Screening.
J.Med.Chem., 54:8563-, 2011

PubMed Abstract: The androgen receptor (AR) is the best studied drug target for the treatment of prostate cancer. While there are a number of drugs that target the AR, they all work through the same mechanism of action and are prone to the development of drug resistance. There is a large unmet need for novel AR inhibitors which work through alternative mechanism(s). Recent studies have identified a novel site on the AR called binding function 3 (BF3) that is involved into AR transcriptional activity. In order to identify inhibitors that target the BF3 site, we have conducted a large-scale in silico screen followed by experimental evaluation. A number of compounds were identified that effectively inhibited the AR transcriptional activity with no obvious cytotoxicity. The mechanism of action of these compounds was validated by biochemical assays and X-ray crystallography. These findings lay a foundation for the development of alternative or supplementary therapies capable of combating prostate cancer even in its antiandrogen resistant forms.

PubMed: 22047606
DOI: 10.1021/JM201098N

Experimental method

X-RAY DIFFRACTION (2.29 Å)